Identification of Common Variants Associated with AIS and Clubfoot

Using exome-sequencing data of >440 AIS patients and >900 controls (in conjunction with >60,000 European controls from the Exome Aggregation Consortium), followed by targeted replication genotyping of top SNPs in >500 additional AIS patients and 1000 controls, we have observed single common variants significantly associated with AIS. One such variant is a missense variant previously associated with a number of physiological characteristics and has led us to interesting hypotheses as to the etiology of at least a proportion of AIS cases. These data are as of yet unpublished, but should be available soon.

We have also used genome-wide common SNP genotyping arrays on a large set of individuals with clubfoot and a large cohort of controls to identify SNPs associated with clubfoot. The strongest evidence of association with clubfoot was found for an intergenic SNP on chromosome 12q24.31 between NCOR2 and ZNF664 (rs7969148, OR=0.58, p=1.25×10⁻⁵) which was significant upon replication (combined OR=0.63, p=1.90×10⁻⁷). Additional suggestive SNPs were identified near FOXN3, SORCS1 and MMP7/TMEM123.